3bf6



Thrombin:suramin complex

Overview
Suramin is a hexasulfonated naphthylurea commonly used as, antitrypanosomial drug and more recently for the treatment of malignant, tumors. Here we show that suramin binds to human alpha-thrombin inhibiting, both the hydrolysis of the synthetic substrate S-2238 (IC50 = 40 microM), and the thrombin-induced fibrinogen clotting (IC50 = 20 microM). The, latter is completely reversed by albumin (30 mg mL(-1)) suggesting that, at therapeutic concentrations, suramin is unable to affect alpha-thrombin, activity in the plasma. Kinetic analysis showed that suramin acts as a, non-competitive inhibitor decreasing Vmax without changing the Km for, S-2238 hydrolysis. Calorimetric studies revealed two distinct binding, sites for suramin in alpha-thrombin. In addition, circular dichroism, studies showed that suramin causes significant changes in alpha-thrombin, tertiary structure, without affecting the secondary structure content., Interaction with alpha-thrombin resulted in an increased fluorescence, emission of the drug. Complex formation was strongly affected by high, ionic strength suggesting the involvement of electrostatic interactions., Altogether our data suggest that part of the biological activities of, suramin might be related to alpha-thrombin inhibition at extra-vascular, sites.

About this Structure
3BF6 is a Protein complex structure of sequences from Homo sapiens with SVR as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference
Suramin interaction with human alpha-thrombin: inhibitory effects and binding studies., Monteiro RQ, Campana PT, Melo PA, Bianconi ML, Int J Biochem Cell Biol. 2004 Oct;36(10):2077-85. PMID:15203120

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